2-74457484-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031288.4(INO80B):c.691G>A(p.Ala231Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000129 in 1,551,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

INO80B
NM_031288.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.11

Publications

0 publications found

Variant links:

Genes affected

INO80B (HGNC:13324): (INO80 complex subunit B) This gene encodes a subunit of an ATP-dependent chromatin remodeling complex, INO80, which plays a role in DNA and nucleosome-activated ATPase activity and ATP-dependent nucleosome sliding. Readthrough transcription of this gene into the neighboring downstream gene, which encodes WW domain-binding protein 1, generates a non-coding transcript. [provided by RefSeq, Feb 2011]

INO80B links:

INO80B-WBP1 (HGNC:49199): (INO80B-WBP1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring INO80B (INO80 complex subunit B) and WBP1 (WW domain-binding protein 1) genes on chromosome 2. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

INO80B-WBP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26314613).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INO80B	NM_031288.4 link	c.691G>A	p.Ala231Thr	missense_variant	Exon 5 of 5	ENST00000233331.12	NP_112578.2	Q9C086
INO80B-WBP1	NR_037849.1 link	n.785G>A		non_coding_transcript_exon_variant	Exon 5 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INO80B	ENST00000233331.12 link	c.691G>A	p.Ala231Thr	missense_variant	Exon 5 of 5	1	NM_031288.4	ENSP00000233331.7		Q9C086
INO80B-WBP1	ENST00000452361.5 link	n.691G>A		non_coding_transcript_exon_variant	Exon 5 of 8	2		ENSP00000388677.1		J3KQ70

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

7.15e-7

AC:

AN:

1399538

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

690920

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31732

American (AMR)

AF:

0.00

AC:

AN:

36102

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25146

East Asian (EAS)

AF:

0.00

AC:

AN:

35960

South Asian (SAS)

AF:

0.00

AC:

AN:

79694

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46686

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5680

European-Non Finnish (NFE)

AF:

9.26e-7

AC:

AN:

1080486

Other (OTH)

AF:

0.00

AC:

AN:

58052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41464

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68038

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 14, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.691G>A (p.A231T) alteration is located in exon 5 (coding exon 5) of the INO80B gene. This alteration results from a G to A substitution at nucleotide position 691, causing the alanine (A) at amino acid position 231 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.63

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.071

Eigen

Benign

-0.090

Eigen_PC

Benign

-0.074

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.037

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.8

PhyloP100

9.1

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.90

REVEL

Benign

0.22

Sift

Benign

0.39

Sift4G

Benign

0.63

Polyphen

0.41

Vest4

0.50

MutPred

0.50

Gain of phosphorylation at A231 (P = 0.0046);

MVP

0.18

MPC

1.6

ClinPred

0.96

GERP RS

3.7

Varity_R

0.22

gMVP

0.61

Mutation Taster

=76/24

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

2-74457484-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over